4-amino-2-chloro-3-fluorobenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of hydroxylamine hydrochloride (336 mg, 4.84 mmol) in water (1.2 mL) was added 4-amino-2-chloro-3-fluorobenzaldehyde (73A) (0.800 g, 4.61 mmol) and pyridine (2.5 mL). After stirring at rt for 1 h, copper (II) sulfate pentahydrate (230 mg, 0.922 mmol) was added followed by a solution of triethylamine (1.40 mL, 9.68 mmol) in CH2Cl2 (2.5 mL). To the resulting dark green reaction mixture was then added a solution of DCC (1.14 g, 5.53 mmol) in CH2Cl2 (10 mL) and the reaction was stirred for 2 h. Formic acid (1 mL) was added and the reaction was stirred for 20 min, filtered through celite, and concentrated. The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane to provide the title compound (0.780 g) as a light brown solid. the reaction was stirred for 2 h the reaction was stirred for 20 min filtered through celite concentrated The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of hydroxylamine hydrochloride (336 mg, 4.84 mmol) in water (1.2 mL) was added 4-amino-2-chloro-3-fluorobenzaldehyde (73A) (0.800 g, 4.61 mmol) and pyridine (2.5 mL). After stirring at rt for 1 h, copper (II) sulfate pentahydrate (230 mg, 0.922 mmol) was added followed by a solution of triethylamine (1.40 mL, 9.68 mmol) in CH2Cl2 (2.5 mL). To the resulting dark green reaction mixture was then added a solution of DCC (1.14 g, 5.53 mmol) in CH2Cl2 (10 mL) and the reaction was stirred for 2 h. Formic acid (1 mL) was added and the reaction was stirred for 20 min, filtered through celite, and concentrated. The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane to provide the title compound (0.780 g) as a light brown solid. the reaction was stirred for 2 h the reaction was stirred for 20 min filtered through celite concentrated The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3-chloro-2-fluoroaniline (10.0 g, 68.7 mmol) in DMSO (500 mL) was added copper (II) chloride (18.5 g, 137.4 mmol) and conc. HCl (50 mL). The whole was heated to 90° C. for 13 h. The reaction was cooled to 0° C. and 4N NaOH was added dropwise to adjust to pH 8. The reaction was diluted with water and extracted with Et2O/EtOAc (1:1). The organic layer was washed with brine, and was dried, filtered and concentrated. The resulting residue was purified via silica gel chromatography eluting with 5-30% EtOAc/hexane to provide 4-amino-2-chloro-3-fluorobenzaldehyde (1.00 g) as a yellow powder. The reaction was cooled to 0° C. extracted with Et2O/EtOAc (1:1) The organic layer was washed with brine was dried filtered concentrated The resulting residue was purified via silica gel chromatography eluting with 5-30% EtOAc/hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of hydroxylamine hydrochloride (336 mg, 4.84 mmol) in water (1.2 mL) was added 4-amino-2-chloro-3-fluorobenzaldehyde (73A) (0.800 g, 4.61 mmol) and pyridine (2.5 mL). After stirring at rt for 1 h, copper (II) sulfate pentahydrate (230 mg, 0.922 mmol) was added followed by a solution of triethylamine (1.40 mL, 9.68 mmol) in CH2Cl2 (2.5 mL). To the resulting dark green reaction mixture was then added a solution of DCC (1.14 g, 5.53 mmol) in CH2Cl2 (10 mL) and the reaction was stirred for 2 h. Formic acid (1 mL) was added and the reaction was stirred for 20 min, filtered through celite, and concentrated. The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane to provide the title compound (0.780 g) as a light brown solid. the reaction was stirred for 2 h the reaction was stirred for 20 min filtered through celite concentrated The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of hydroxylamine hydrochloride (336 mg, 4.84 mmol) in water (1.2 mL) was added 4-amino-2-chloro-3-fluorobenzaldehyde (73A) (0.800 g, 4.61 mmol) and pyridine (2.5 mL). After stirring at rt for 1 h, copper (II) sulfate pentahydrate (230 mg, 0.922 mmol) was added followed by a solution of triethylamine (1.40 mL, 9.68 mmol) in CH2Cl2 (2.5 mL). To the resulting dark green reaction mixture was then added a solution of DCC (1.14 g, 5.53 mmol) in CH2Cl2 (10 mL) and the reaction was stirred for 2 h. Formic acid (1 mL) was added and the reaction was stirred for 20 min, filtered through celite, and concentrated. The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane to provide the title compound (0.780 g) as a light brown solid. the reaction was stirred for 2 h the reaction was stirred for 20 min filtered through celite concentrated The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3-chloro-2-fluoroaniline (10.0 g, 68.7 mmol) in DMSO (500 mL) was added copper (II) chloride (18.5 g, 137.4 mmol) and conc. HCl (50 mL). The whole was heated to 90° C. for 13 h. The reaction was cooled to 0° C. and 4N NaOH was added dropwise to adjust to pH 8. The reaction was diluted with water and extracted with Et2O/EtOAc (1:1). The organic layer was washed with brine, and was dried, filtered and concentrated. The resulting residue was purified via silica gel chromatography eluting with 5-30% EtOAc/hexane to provide 4-amino-2-chloro-3-fluorobenzaldehyde (100 g) as a yellow powder. The reaction was cooled to 0° C. extracted with Et2O/EtOAc (1:1) The organic layer was washed with brine was dried filtered concentrated The resulting residue was purified via silica gel chromatography eluting with 5-30% EtOAc/hexane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of hydroxylamine hydrochloride (336 mg, 4.84 mmol) in water (1.2 mL) was added 4-amino-2-chloro-3-fluoro-benzaldehyde (9A) (0.800 g, 4.61 mmol) and pyridine (2.5 mL). After stirring at rt for 1 h, copper (H) sulfate pentahydrate (230 mg, 0.922 mmol) was added followed by a solution of triethylamine (1.40 mL, 9.68 mmol) in CH2Cl2 (2.5 mL). To the resulting dark green reaction mixture was then added a solution of DCC (1.14 g, 5.53 mmol) in CH2Cl2 (10 mL) and the reaction was stirred for 2 h. Formic acid (1 mL) was added and the reaction was stirred for 20 min, filtered through celite, and concentrated. The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane to provide the title compound (0.780 g) as a light brown solid. the reaction was stirred for 2 h the reaction was stirred for 20 min filtered through celite concentrated The resulting residue was purified via silica gel chromatography eluting with 20-30% EtOAc/hexane

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3-chloro-2-fluoroaniline (10.0 g, 68.7 mmol) in DMSO (500 mL) was added copper (II) chloride (18.5 g, 137.4 mmol) and conc. HCl (50 mL). The whole was heated to 90° C. for 13 h. The reaction was cooled to 0° C. and 4N NaOH was added dropwise to adjust to pH 8. The reaction was diluted with water and extracted with Et2O/EtOAc (1:1). The organic layer was washed with brine, and was dried, filtered and concentrated. The resulting residue was purified via silica gel chromatography eluting with 5-30% EtOAc/hexane to provide 4-amino-2-chloro-3-fluoro-benzaldehyde (1.00 g) as a yellow powder. The reaction was cooled to 0° C. extracted with Et2O/EtOAc (1:1) The organic layer was washed with brine was dried filtered concentrated The resulting residue was purified via silica gel chromatography eluting with 5-30% EtOAc/hexane